Ammonium Chloride → HCID 71008574, compound

HRID 337294Notes

Reaction equation

HRID 337294 reaction equation
[N:1]1([CH2:5][C:6]([CH3:16])([O:8][C:9]2[CH:10]=[CH:11][C:12](Cl)=[N:13][CH:14]=2)[CH3:7])[CH2:4][CH2:3][CH2:2]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C[Si]([N-:46][Si](C)(C)C)(C)C.[Li+].[NH4+].[Cl-]>O1CCCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:1]1([CH2:5][C:6]([CH3:16])([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH2:46])=[N:13][CH:14]=2)[CH3:7])[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 71739075HCID 71739075, compound

Product 1

HCID 71008574HCID 71008574, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
75 °C

Procedure

5-(1-(azetidin-1-yl)-2-methylpropan-2-yloxy)-2-chloropyridine (3.5 g, 14.5 mmol, Eq: 1.00) was dissolved in tetrahydrofuran (78.0 ml). 2-(Dicyclohexylphosphino)biphenyl (1.02 g, 2.91 mmol, Eq: 0.2), then tris(dibenzylideneacetone)dipalladium(0) (1.33 g, 1.45 mmol, Eq: 0.1) were added under an argon atmosphere. Finally 1M lithium bis(trimethylsilyl)amide in THF (43.6 ml, 43.6 mmol, Eq: 3) was added dropwise. The reaction mixture was stirred under argon atmosphere at 75° C. over night. The reaction mixture was poured into 100 ml saturated NH4Cl and extracted with EtOAc (100 ml). The organic phase and washed with 50% diluted brine. The aqueous phase was back extracted with 2×80 ml EtOAc. The combined organic phase was dried (MgSO4), filtered and concentrated in vacuo. The crude material was purified by Analogix MPLC (40 g column (eluted with 1% to 10% MeOH in DCM) to afford the desired product (1.66 g) as a brown viscous oil. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.18 (s, 6 H) 2.10 (quin, J=7.08 Hz, 2 H) 2.54 (s, 2 H) 3.33 (t, J=6.99 Hz, 4 H) 4.25 (br. s., 2 H) 6.43 (d, J=8.69 Hz, 1 H) 7.12 (dd, J=8.69, 2.64 Hz, 1 H) 7.79 (d, J=2.64 Hz, 1 H).

Workup

  1. extractionextracted with EtOAc (100 ml)
  2. washThe organic phase and washed with 50% diluted brine
  3. extractionThe aqueous phase was back extracted with 2×80 ml EtOAc
  4. dry with materialThe combined organic phase was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by Analogix MPLC (
  8. wash40 g column (eluted with 1% to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-08a841df16d14a3eaa49890d993cebb5
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

Loading…